Many accidental and occupational radiation exposures involve both deposition of radioactive material and acute external exposure. This produces a range or unique exposure patterns to radiation with both high and low linear energy transfer (LET). These unique exposure patterns can alter the sensitivity of cells to the induction of cancer and genetic damage and modify carcinogenic and genetic risk. Recent research in vitro has demonstrated that low doses of low LET ionizing radiation reduces the frequency of chromatid aberrations induced by subsequent radiation exposure. It was also demonstrated that radiation in late stages of the cell cycle of transformed cells or of cells from individuals with genetic predisposition to cancer produces a large increase in the frequency of chromatid aberrations above those observed in normal cells. The two hypotheses tested in this proposal are that: 1) Radiation exposure from internally deposited radioactive materials in vivo decreases the sensitivity of chromosomes in normal cells to subsequent x-ray exposure. 2) Abnormal cells, which result from low dose rate irradiation from internally deposited radioactive materials, have increased x-ray sensitivity for the induction of chromatid aberrations. These hypotheses will be tested by measuring the radiation sensitivity of chromosomes in epithelial cells of the Chinese hamster liver. The measure will be made as a function of the stage of the cell cycle, LET of internally deposited radioactive materials, and histological stages of cellular progress from normal to cancer cells. The specific aims of this study address the proposed hypotheses by answering three questions. First, what is the relative biological effectiveness of protracted high and low LET radiation for the induction of chromosome aberrations from internally deposited radioactive materials? Second, what is the influence of internally deposited radioactive material with different LET on the radiation sensitivity of the liver cells to the induction of aberrations? Third, how does the radiation sensitivity of the chromosomes change in cells exposed to internally deposited radioactive materials as the cells progress from normal to hyperplastic nodules and on to a neoplastic state?